Ribosome–premature termination codon translation complex (PTC-ribosome complex)

The ribosome–premature termination codon (PTC) translation complex is a specialized ribonucleoprotein assembly that forms when a ribosome encounters a nonsense mutation within an mRNA sequence (Keeling et al., 2014, Critical Reviews in Biochemistry and Molecular Biology). Under normal physiological conditions, this complex facilitates the premature termination of translation and triggers the nonsense-mediated mRNA decay (NMD) pathway to eliminate defective transcripts (Linde and Kerem, 2008, Trends in Genetics). In the context of genetic diseases, this process prevents the synthesis of full-length, functional proteins, leading to severe clinical phenotypes such as those seen in cystic fibrosis and Duchenne muscular dystrophy (Bidou et al., 2012, Gene). This complex is a primary target for nonsense suppression therapy, which utilizes small molecules to modulate ribosomal decoding at the A-site. These drugs, such as ataluren and ELX-02, interact with the ribosome within this complex to promote the incorporation of a near-cognate tRNA at the PTC (Welch et al., 2007, Nature). This "read-through" mechanism allows the ribosome to bypass the stop signal and complete the synthesis of a full-length, functional protein. Successful targeting of this complex offers a mutation-specific approach to treating a wide array of inherited disorders caused by premature stop codons.

Other names

Premature termination codon-stalled ribosomePTC-containing translation complexNonsense mutation-stalled translation complexPTC-ribosome assembly

Translational read-through induction (nonsense suppression)